Ab Initio correlated all electron dirac-fock calculations for Eka-Francium Fluoride (E119F)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the adequacy of diflubenzuron and dechlorane in toxic baits for leaf-cutting ants (Hymenoptera : Formicidae) based on formicidal activity

Studies assessing the characteristics of active ingredients (AIs) of toxic baits for leaf-cutting ants are still scarce, although the need for a delayed action of these compounds on adult workers has been well accepted (mortality <= 15% at 24 h and <= 90% at 21 days). Therefore, we determined the insecticidal action of two AIs used in commercial baits, diflubenzuron and dechlorane, over time in workers, and discussed the control of colonies in relation to the existing literature. Dechlorane presented excellent insecticidal activity with a delayed action at all concentrations tested, although its commercial use has been prohibited due to its organochlorine nature. In contrast, diflubenzuron did not cause significant mortality or symptoms of intoxication, indicating that the successful cases reported with the use of baits containing this AI were in fact due to an accidental contamination with dechlorane. We comment about the ineffectiveness of diflubenzuron on alternative targets, i.e., young forms and the mutualistic fungus, supporting the concept that the AI needs to a have a delayed action on adult workers.

Identification and expression analysis of microRNAs and targets in the biofuel crop sugarcane

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular models of protein targets from Mycobacterium tuberculosis

Structural characterization of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design since some of these proteins may be present in the bacterial genome, but absent in humans. Thus, metabolic pathways became potential targets for drug design. The motivation of this work is the fact that Mycobacterium tuberculosis is the cause of the deaths of millions of people in the world, so that the structural characterization of protein targets to propose new drugs has become essential. DBMODELING is a relational database, created to highlight the importance of methods of molecular modeling applied to the Mycobacterium tuberculosis genome with the aim of proposing protein-ligand docking analysis. There are currently more than 300 models for proteins from Mycobacterium tuberculosis genome in the database. The database contains a detailed description of the reaction catalyzed by each enzyme and their atomic coordinates. Information about structures, a tool for animated gif image, a table with a specification of the metabolic pathway, modeled protein, inputs used in modeling, and analysis methods used in this project are available in the database for download. The search tool can be used for reseachers to find specific pathways or enzymes.

The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Monte Carlo and analytical calculation of lateral deflection of proton beams in homogeneous targets

Proton radiation therapy is a precise form of radiation therapy, but the avoidance of damage to critical normal tissues and the prevention of geographical tumor misses require accurate knowledge of the dose delivered to the patient and the verification of his position demand a precise imaging technique. In proton therapy facilities, the X-ray Computed Tomography (xCT) is the preferred technique for the planning treatment of patients. This situation has been changing nowadays with the development of proton accelerators for health care and the increase in the number of treated patients. In fact, protons could be more efficient than xCT for this task. One essential difficulty in pCT image reconstruction systems came from the scattering of the protons inside the target due to the numerous small-angle deflections by nuclear Coulomb fields. The purpose of this study is the comparison of an analytical formulation for the determination of beam lateral deflection, based on Molière's theory and Rutherford scattering with Monte Carlo calculations by SRIM 2008 and MCNPX codes. © 2010 American Institute of Physics.

Unravelling the Neospora caninum secretome through the secreted fraction (ESA) and quantification of the discharged tachyzoite using high-resolution mass spectrometry-based proteomics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular expression profile reveals potential biomarkers and therapeutic targets in canine endometrial lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)